Part I.

Introduction to Molecular Modeling

1. What is molecular modeling
Model is some kind of a representation of a system, usually simplified, that allows for description,
investigation and prediction of properties of interest.
Molecular modeling, which is more or less synonymous with computational chemistry, is a
discipline concerned with developing models of molecular systems, chemical reactions and
phenomena of interest to chemistry.
Why chemists use models:
a) to help with analysis and interpretation of experimental data
b) to uncover new laws and formulate new theories
c) to help solve problems and hint solutions before doing experiments
d) to help design new experiments
e) to predict properties and quantities that are difficult or even impossible to observe
experimentally
Simulations and computer “experiments” can be designed to mimic reality, however, are always
based on assumptions, approximations and simplifications (i.e. models).
Important characteristics of models are:
a) Level of simplification: very simple to very complex
b) Generality: general or specific, i.e. relate only to specific systems or problems
c) Limitations: one must always be aware of the range of applicability and limits of accuracy
of any model.
d) Cost and efficiency: CPU time, memory, disk space
Computable quantities:
a) molecular structures: closely tied to energy (best structure - one for which the energy is
minimum)
b) energy: potential energy surfaces (PES) - extremely important! PES dictate essentially
everything about the molecule or system
c) molecular properties that can be compared to/used to interpret experiments:
thermodynamics, kinetics, spectra (IR, UV, NMR)
d) properties that are not experimental observables: bond order, aromaticity, molecular
orbitals ….
2. Model chemistries
Molecular modeling (a.k.a. computational chemistry) is based on numerically (on the computer)
solving the equations that express fundamental physical laws. This can be done at various levels:
we talk about “levels of theory” or “model chemistries”
2.1. Quantum mechanics
Quantum mechanics, also electronic structure methods, are the most fundamental level of theory
at which molecules can be treated. In seeks the solution to the Schrodinger equation:

Hˆ   E (1)

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The price one pays is that the equation cannot be solved exactly and, as we will see, drastic
approximations are often required. Even such approximate solutions can be difficult and
computationally expensive and are generally limited to small molecules or systems.
The specific approximations used in solutions define the more specific “level of theory” or “model
chemistry” used.
The basic classification of quantum mechanical methods is:
a) Semi-empirical methods
b) Ab initio methods
c) Density functional theory (DFT) methods
d) Compound methods
The specific level of theory is defined by the combination of the theoretical method (which can be
roughly thought of as the approximation to the Hamiltonian Ĥ in eqn. 1), and the basis set, (which
is an approximation for the wavefunction  ). For example, HF/6-31G(d) level of theory is
Hartree-Fock method with 6-31G(d) basis set. Semiempirical methods use default basis set and
the Hamiltonian alone defined the level, for example CNDO. Density functional methods are
specified by different density functionals (e.g. BLYP with the same basis set would give BLYP/6-
31G(d) level).
Another important component to specify, though not strictly a part of the model chemistry, is
whether the calculation is spin restricted or unrestricted. This defines how electrons with different
spins are handled: for closed shell systems, where all orbitals are doubly occupied by electrons
with opposite spins the restricted calculations are done. For open shell systems, such as radicals,
excited states etc., unrestricted spin model is usually used and specified with an “U”: e.g. UHF/6-
31G(d).
2.2. Molecular mechanics
Molecular mechanics methods are based on the laws of classical physics. They do not explicitly
treat the electrons: the electronic effects, such as chemical bonds, are included implicitly in the
energy function, known as the force field, which describes the interactions between the nuclei only.
As such, the molecular mechanics methods can be viewed as a “coarse-grained” model: the
electrons are lumped into empirical parameters.
Molecular mechanics methods are characterized by the force fields, many of which have been
parameterized. The advantage of molecular mechanics methods is much higher computational
efficiency, which allows modeling of very large systems with many atoms, simulations of
molecular ensembles etc. The main disadvantages are that a) the force fields are typically limited
to specific classes of molecules for which they were parameterized, and b) since electrons are not
treated, properties that depend on details of the electronic structure cannot be modeled. This
primarily involves chemical reactions in which bonds are formed and/or broken.
2.3. Hybrid QM/MM methods
Hybrid methods try to overcome the limitations of quantum and classical methods by combining
them. In such model chemistry, a part (small) of the system that may undergo reactions is treated
at quantum mechanical level, which the rest (large) is treated classically using a force field.
Different schemes can be used to model the interactions between the quantum and classical parts.

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3. Units
Proper units are an essential part of specifying and reporting of any physical quantity. To get any
meaningful results from computational modeling (as from experiments) one needs to know how
to use and convert units. Computational chemistry, in particular quantum, often uses so called
atomic units, but not exclusively. Angstroms (10-10 m), calorie based energy units (in particular
cal/mol) are common as are wavenumbers (cm-1), cgs units (Debye) and others. Some commonly
encountered units and conversions are given in the tables below.

Fundamental atomic units

Dimension Name Symbol Value in SI units
mass electron rest mass me 9.1093826(16)×10−31 kg
charge elementary charge e 1.60217653(14)×10−19 C
angular momentum Reduced Planck's constant ħ = h/2 1.05457168(18)×10−34 J·s
electric constant Coulomb force constant 1 / (4πε0) 8.9875517873681×109 kg·m3·s-2·C-2

Derived atomic units

Value in more
Dimension Name Symbol Expression Value in SI units
common units
Bohr 0.052918 nm
length a0 4πε0ħ2/(mee2)= ħ/(mec) 5.291772108(18)×10−11 m
radius =0.52918 Å
Hartree
energy Eh mee4/(4πε0ħ)2 4.35974417(75)×10−18 J 27.211 eV
energy
time ħ/Eh 2.418884326505(16)×10−17 s
velocity a0Eh/ħ = c 2.1876912633(73)×106 m·s−1
82.387 nN
force Eh/a0 8.2387225(14)×10−8 N
=51.421 eV·Å−1
temperature Eh/kB 3.1577464(55)×105 K 27.211 eV
pressure Eh/a03 2.9421912(19)×1013 Pa
electric 514.21 V·nm−1
Eh/(ea0) 5.1421×1011 V·m−1
field =51.421 V·Å−1

Other units often used in (computational) chemistry

Name Quantity Symbol Value in SI
calorie energy cal 4.184 J
wavenumber frequency
cm-1 102 m-1
(inverse centimeter) (inverse of wavelength)
atomic mass unit mass amu 1.660 538 782(83)×10−27 kg
Ångström length Å 10-10 m